Btobioinnovation.com 

Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com 

SPECIAL REPORT #22.5

Stroke

Stroke ranks as the third cause of death in the world after ischaemic heart disease and the cumulative cancer diseases. Each year, about 20 million strokes occur in the world causing a total of 7.2 million death. Stroke is a global epidemic which affects all types of countries. A study published in 2009 stated that unexpectedly about 85% of all stroke deaths occur in low- and middle- income countries.  Age is recognised as the most relevant risk factor associated with stroke. With a fast-growing ageing population around the globe, the number of persons at risk is also increasing.

The economic and societal burden of stroke is extremely high with direct and indirect costs estimated at more than €60 billion in the European Union and at $103 billion in the U.S. Three months after a stroke, 17% of patients have died, 54% still have moderate to severe disability and only 29% went back to normal living. Disability induced by stroke often requires adapted assistance for daily care over several months.

The sooner signs of onset of stroke are recognised and treated the better the overall outcome will be for a given patient.

The acronym “FAST” is useful to help remember the symptoms:

• Facial drooping: the face is paralysed and drooping
• Arm weakness: the patient can hardly lift his arms or legs
• Speech deficiency: the patient speech is lured
• Time: call the emergency services immediately

There are two types of stroke.

• The ischaemic stroke is caused by a clot, often called thrombus, that obstructs a cerebral artery and inhibits the blood flow to a given region of the brain. The main causes of ischaemic stroke are due to atherosclerosis and atrial fibrillation.
• The haemorrhagic stroke is caused by a blood vessel that ruptures and subsequently prevents blood flow to part of the brain. The main underlying cause of haemorrhagic stroke is high blood pressure.

A transient ischaemic stroke or TIA is caused by a temporary clot. Whatever occurs, in all these cases, brain cells close to the injured area are being oxygen deprived and begin to die or are being severely damaged.

80 to 85% of all strokes are of the ischaemic type. The primary goal for the acute treatment of ischaemic stroke patients is to restore as rapidly as possible blood flow to the injured brain area in order to protect as much as possible healthy tissues and help damaged area to recover. The longer brain tissues are deprived of oxygen and nutrients the greater patients are at risk of a fatal issue or of a permanent brain damage. Acute treatments for ischaemic stroke include thrombosis and drug therapies to break down the thrombus.

Acute haemorrhagic stroke affects around 350,000 patients yearly. The current treatment, called thrombectomy, consists of a surgical procedure aimed at physically removing the clot with unfortunately a rather poor clinical outcome. Intensive nursing and monitoring have also been deceptive. As a consequence, 75% of acute haemorrhagic stroke patients die or suffer from severe disability. Nevertheless, in the recent MisTIE program, clinicians showed that there was a strong relationship between the volume of haematoma evacuated with the use of ateplase, the gold standard thrombolytic agent, and the level of handicap one year after treatment.

Two French companies are currently trying to bring new solutions to the two types of strokes.

Acticor, based in Paris, is developing Glenzocimab, a monoclonal antibody which targets the platelet glycoprotein VI, a platelet membrane protein which belongs to the immunoglobulin superfamily. Glycoprotein VI (GPVI) is expressed exclusively by platelets and is a key receptor on platelets for binding fibrin, fibrinogen and collagen. Interactions between GPVI and its different ligands triggers platelet activation leading to aggregation, additional platelets recruitment and clot formation. Targeting GPVI becomes an attractive antithrombotic strategy without the risk of major bleeding. Acticor is currently conducting two clinical phase 1b/2a studies: Actimis as an add-on therapy to standard of care and Actisave as an add-on therapy to thrombolysis. The regimen consists of a 6-hour intravenous infusion of glenzocimab to cover the duration of the acute phase and initiated within the first 4.5 hours after the onset of stroke symptoms. On February 23, Acticor reported positive results from its Actimis clinical trial conducted in Europe which included 166 patients. On October 29, 2021, Acticor announced a successful IPO on EuroNext when it raised €15.5 million. In July 2018, Acticor had signed a €60 million regional development and commercialisation agreement with CMS Medical Limited from China with exclusive rights for greater China.

Op2Lysis, based in Caen (France) and in Liège (Belgium) is developing O2L-001, a nanoparticule formulation of an engineered ateplase, OptPA which is an effective and safe treatment to remove intracerebral haematoma and reduce disability and death. O2L-001 is locally injected in the brain, through micro-invasive surgery via a catheter at the core of the haematoma. O2L-001 is easy to use via a unique injection, has a better thrombolytic effect than the gold standard and is expected to induce less side effects. The product is in late-stage preclinical development. Op2Lysis has been named an innovative company by Medicen – the Paris Region Biocluster- in 2017, awarded with the Special Jury Prize at the Biovision and the Winner of the Netva and ILAB competions. Op2Lysis has received funding from business angels, WiSEED, a crowdfunding platform, BPI, the French Public Investment Bank and Noshaq, an investment fund located in Liège. On November 9, 2021, the US Food and Drug Administration has granted Orphan Drug Designation to OptPA for the treatment of intracerebral haemorrhage. The company has recently been selected for blended funding (grant and capital) by the European Innovation Council accelerator of the Horizon Europe funding program and is currently actively involved in raising funds to launch its clinical trial.

Paris, February 29, 2022.

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